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10 pages, 273 KB  
Article
Prevalence and Specificity of Anti-HPA and Anti-HLA Antibodies in Patients with Suspected Immune-Mediated Platelet Disorders: A Single-Center Study from Serbia
by Svetlana Vojvodić and Jasmina Grujić
Medicina 2026, 62(4), 725; https://doi.org/10.3390/medicina62040725 (registering DOI) - 10 Apr 2026
Abstract
Background and Objectives: Alloantibodies directed against human platelet antigens and human leukocyte antigens are implicated in several immune-mediated platelet disorders, including platelet transfusion refractoriness, post-transfusion purpura and fetal and neonatal alloimmune thrombocytopenia. Reliable and simultaneous detection of these antibodies is essential for accurate [...] Read more.
Background and Objectives: Alloantibodies directed against human platelet antigens and human leukocyte antigens are implicated in several immune-mediated platelet disorders, including platelet transfusion refractoriness, post-transfusion purpura and fetal and neonatal alloimmune thrombocytopenia. Reliable and simultaneous detection of these antibodies is essential for accurate diagnosis and appropriate clinical management. The aim of this study was to determine the prevalence and specificity spectrum of anti-HLA and anti-HPA alloantibodies in patients with suspected immune-mediated platelet disorders using a multiplex bead-based assay, and to evaluate its diagnostic utility in a Serbian cohort. Materials and Methods: A bead-based glycoprotein-specific antibody detection assay was performed using monoclonal antibodies specific for platelet glycoproteins and HLA class I molecules, separately coupled to Luminex microbeads. Serum samples were collected from 259 patients, including 234 patients with thrombocytopenia, 11 with neonatal alloimmune thrombocytopenia, and 14 with suspected platelet transfusion refractoriness. All samples were tested using the PakLx Luminex assay, and results were interpreted with MatchIt! Antibody software. Results: Of the 259 tested samples, 72 (27.8%) were positive for HLA and/or platelet-specific antibodies. Among the positive samples, 29.2% contained HLA class I antibodies, 45.8% contained platelet-specific antibodies, and 25% showed combined HLA and platelet antibody positivity. The most frequently detected platelet-specific antibodies were directed against GPIIb/IIIa (HPA-1, -3, -4) and GPIa/IIa (HPA-5). Conclusions: This first analysis of platelet alloantibodies in a Serbian cohort demonstrates a high prevalence of antibody positivity in patients with neonatal alloimmune thrombocytopenia and platelet transfusion refractoriness, with anti-HPA-1a as the predominant specificity. The significant association between clinical presentation and antibody profile underscores the need for targeted diagnostic testing. Multiplex bead-based technology provides comprehensive alloantibody detection, facilitating optimized transfusion management in immune-mediated platelet disorders. Full article
(This article belongs to the Section Hematology and Immunology)
32 pages, 2513 KB  
Article
A Sustainability-Oriented Framework for Evaluating the “Hardcore Strength” of World-Class Ports: Multi-Dimensional Indicators and Game-Theoretic Weight Integration
by Xiangzhi Jin, Xiwen Lou, Wenbo Su, Manel Grifoll, Zhengfeng Huang, Guiyun Liu and Pengjun Zheng
Sustainability 2026, 18(8), 3751; https://doi.org/10.3390/su18083751 (registering DOI) - 10 Apr 2026
Abstract
Building world-class ports requires not only scale expansion but also sustainable structural capability. However, the concept of port “hardcore strength” remains insufficiently clarified and operationalized in existing sustainability and port evaluation research. In this study, port hardcore strength is understood as an integrated [...] Read more.
Building world-class ports requires not only scale expansion but also sustainable structural capability. However, the concept of port “hardcore strength” remains insufficiently clarified and operationalized in existing sustainability and port evaluation research. In this study, port hardcore strength is understood as an integrated capability framework covering infrastructure efficiency and logistics capability, connectivity and regional integration, maritime services and industrial clustering, strategic leadership and innovation capability, and sustainable governance and green port development. This study proposes a sustainability-oriented evaluation framework for assessing the “hardcore strength” of world-class ports through a multi-dimensional indicator system. Methodologically, the study integrates the EWM and CRITIC, and introduces Bland–Altman analysis to examine whether the EWM and CRITIC weight vectors exhibit an obvious systematic bias prior to game-theoretic integration. Using 18 representative global ports from 2019 to 2023 as a case study, the results show that the overall ranking structure remains broadly stable, with Singapore Port and Shanghai Port consistently ranking first and second, respectively, while some middle-ranked ports exhibit moderate positional changes. The findings suggest that differences in world-class port development are rooted not only in operational scale, but also in the coordination of multiple capability dimensions. The study enriches the understanding of world-class port evaluation from a sustainability-oriented perspective. Full article
(This article belongs to the Section Sustainable Transportation)
26 pages, 1385 KB  
Article
Probabilistic Short-Term Sky Image Forecasting Using VQ-VAE and Transformer Models on Sky Camera Data
by Chingiz Seyidbayli, Soheil Nezakat and Andreas Reinhardt
J. Imaging 2026, 12(4), 165; https://doi.org/10.3390/jimaging12040165 (registering DOI) - 10 Apr 2026
Abstract
Cloud cover significantly reduces the electrical power output of photovoltaic systems, making accurate short-term cloud movement predictions essential for reliable solar energy production planning. This article presents a deep learning framework that directly estimates cloud movement from ground-based all-sky camera images, rather than [...] Read more.
Cloud cover significantly reduces the electrical power output of photovoltaic systems, making accurate short-term cloud movement predictions essential for reliable solar energy production planning. This article presents a deep learning framework that directly estimates cloud movement from ground-based all-sky camera images, rather than predicting future production from past power data. The system is based on a three-step process: First, a lightweight Convolutional Neural Network segments cloud regions and produces probabilistic masks that represent the spatial distribution of clouds in a compact and computationally efficient manner. This allows subsequent models to focus on the geometry of clouds rather than irrelevant visual features such as illumination changes. Second, a Vector Quantized Variational Autoencoder compresses these masks into discrete latent token sequences, reducing dimensionality while preserving fundamental cloud structure patterns. Third, a GPT-style autoregressive transformer learns temporal dependencies in this token space and predicts future sequences based on past observations, enabling iterative multi-step predictions, where each prediction serves as the input for subsequent time steps. Our evaluations show an average intersection-over-union ratio of 0.92 and a pixel accuracy of 0.96 for single-step (5 s ahead) predictions, while performance smoothly decreases to an intersection-over-union ratio of 0.65 and an accuracy of 0.80 in 10 min autoregressive propagation. The framework also provides prediction uncertainty estimates through token-level entropy measurement, which shows positive correlation with prediction error and serves as a confidence indicator for downstream decision-making in solar energy forecasting applications. Full article
(This article belongs to the Special Issue AI-Driven Image and Video Understanding)
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14 pages, 461 KB  
Article
Association of Once-Daily MALDI-TOF MS Identification with Antibiotic Appropriateness and First-Modification Patterns in Emergency Department Bacteremia: A Retrospective Before–After Cohort Study
by Jack Yu-Shuo Lu, Yu-Hsun Wang, Shu-Ling Tzeng, Yuan-Ti Lee and Tzu-Chi Wu
Antibiotics 2026, 15(4), 386; https://doi.org/10.3390/antibiotics15040386 - 10 Apr 2026
Abstract
Background: Blood cultures are frequently obtained in the emergency department (ED), yet organism identification and subsequent antibiotic optimization commonly occur after hospital admission. Inappropriate empiric therapy remains common and is associated with adverse outcomes. MALDI-TOF MS can shorten the time to organism identification; [...] Read more.
Background: Blood cultures are frequently obtained in the emergency department (ED), yet organism identification and subsequent antibiotic optimization commonly occur after hospital admission. Inappropriate empiric therapy remains common and is associated with adverse outcomes. MALDI-TOF MS can shorten the time to organism identification; however, real-world effectiveness may depend on laboratory cadence and stewardship support, and evidence for once-daily batch workflows without active antimicrobial stewardship is limited. Method: We performed a retrospective before–after cohort study at a tertiary medical center in central Taiwan, comparing positive blood cultures (PBCs) obtained in the ED before MALDI-TOF MS implementation (1 May–31 July 2018; conventional identification) and after implementation (1 September–30 November 2018; MALDI-TOF MS). Primary endpoints were appropriate antibiotic therapy at 24, 48, and 72 h after the first PBC report. Secondary endpoints included timing, location, and classification (escalation vs. de-escalation) of the first antibiotic modification. Results: After exclusions, 323 unique PBCs were analyzed (182 pre-implementation; 141 post-implementation). Baseline characteristics and clinical outcomes were similar, including in-hospital mortality (14.8% vs. 14.9%). Time to the initial positive report (Gram stain) and the final report (identification with antimicrobial susceptibility testing) did not differ significantly between periods. Appropriate antibiotic use at 24/48/72 h was comparable (75.3% vs. 76.6%, 82.4% vs. 80.1%, and 86.3% vs. 84.4%). The timing and pattern of the first antibiotic modification were also similar. In a secondary stratified analysis, patients modified before culture positivity had higher acuity and worse outcomes. Conclusions: Once-daily MALDI-TOF MS implementation was not associated with improved antibiotic appropriateness or modification patterns in ED bacteremia without active real-time stewardship oversight. Higher-frequency processing and real-time stewardship linkage may be required to translate faster diagnostics into timely therapeutic action. Full article
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28 pages, 2313 KB  
Article
Application of Generative Artificial Intelligence for Innovative Teaching
by Nikola Kadoić, Jelena Gusić Munđar and Tena Jagačić
Appl. Sci. 2026, 16(8), 3699; https://doi.org/10.3390/app16083699 - 9 Apr 2026
Abstract
There are numerous ways in which generative artificial intelligence (GAI) can be applied in the teaching and learning process. This paper presents one application in the Business Decision Analysis (BDA) course. BDA is considered as the most challenging course in the Graduate Study [...] Read more.
There are numerous ways in which generative artificial intelligence (GAI) can be applied in the teaching and learning process. This paper presents one application in the Business Decision Analysis (BDA) course. BDA is considered as the most challenging course in the Graduate Study Program in Economic Entrepreneurship at the University of Zagreb Faculty of Organisation and Informatics; consequently, the teachers continuously analyse possibilities to make the course more attractive for students. The innovative teaching activity at BDA was implemented as a betting shop during the first colloquium (which accounts for 50% of the overall grade). In the activity, GAI analysed learning management system (LMS) data of students’ results (attendance, self-assessment test results, logs in the system) of the initial (pre-course) test, as well as their results of the pub quiz (activity organised a week before the colloquium as a preparatory activity). GAI analysed all the data and predicted the number of points each student will achieve. Additionally, GAI calculated the risk index, average growth (among self-assessment tests) and learning consistency for each student. Finally, GAI created a message for each student that explained what went well in their learning activity, what could be improved, and included a motivational note for the test. The rule was: if a student achieved a higher result than the GAI predicted, the teacher would buy a chocolate for that student. More than 60% percent of students achieved a higher score than was predicted. Surprisingly, exceeding the expected result was not in correlation with the risk indices determined by the GAI. Cluster analysis identified four student profiles consistent with the correlation results, showing weak overall agreement between the predicted and achieved scores, except in the male subgroup, while higher predicted scores were associated with higher average growth and lower risk indices. Qualitative analysis of the GAI application in teaching yielded positive comments, as students perceived the activity as helpful, motivating, and engaging, and would have liked more similar activities. Full article
12 pages, 268 KB  
Article
Optimal Range of k-Consecutive Sums on a Circle for n = 2k + 1 and n = k2 + 1
by Yaoran Yang and Yutong Zhang
Mathematics 2026, 14(8), 1252; https://doi.org/10.3390/math14081252 - 9 Apr 2026
Abstract
Arrange the integers 1,2,,n on a circle and, for a fixed k1, let si be the sum of the k consecutive entries starting at position i (indices taken modulo n). For a [...] Read more.
Arrange the integers 1,2,,n on a circle and, for a fixed k1, let si be the sum of the k consecutive entries starting at position i (indices taken modulo n). For a circular permutation π, define the range R(π)=maxisiminisi, and let w(n,k) be the minimum value of R(π) over all circular permutations of {1,,n}. We obtain three structural results. First, we prove the complement symmetry w(n,k)=w(n,nk). Second, we determine the first nontrivial arithmetic progression case n=2k+1 exactly: w(2k+1,k)=2k2. Third, we determine the structured regime n=k2+1 exactly: w(k2+1,k)=k. The proofs combine averaging lower bounds on the progression n1(modk) with explicit constructions: a parity-sensitive two-block arrangement for n=2k+1 and a k×k array construction for n=k2+1. Full article
(This article belongs to the Special Issue New Perspectives of Graph Theory and Combinatorics)
18 pages, 1434 KB  
Review
Therapeutic Endoscopic Ultrasound in Biliopancreatic Disease
by Aurelio Mauro, Carlotta Crisciotti, Giulio Massetti, Daniele Alfieri, Stefano Mazza, Davide Scalvini, Alessandro Cappellini, Guglielmo Aprile, Gianmaria La Rosa, Francesca Torello Viera, Letizia Veronese, Marco Bardone and Andrea Anderloni
J. Clin. Med. 2026, 15(8), 2848; https://doi.org/10.3390/jcm15082848 - 9 Apr 2026
Abstract
Therapeutic endoscopic ultrasound (t-EUS) has transformed the management of biliopancreatic diseases by enabling minimally invasive access and intervention through the gastrointestinal wall. This narrative review summarizes current indications and evolving roles of t-EUS in benign and malignant biliary disease, with a focus on [...] Read more.
Therapeutic endoscopic ultrasound (t-EUS) has transformed the management of biliopancreatic diseases by enabling minimally invasive access and intervention through the gastrointestinal wall. This narrative review summarizes current indications and evolving roles of t-EUS in benign and malignant biliary disease, with a focus on the different modalities of transmural drainage, EUS-guided gastroenterostomy (EUS-GE), and EUS-guided radiofrequency ablation (EUS-RFA). In benign settings, EUS-gallbladder drainage (EUS-GBD) has emerged as a minimally invasive alternative to percutaneous cholecystostomy for high-risk patients with acute cholecystitis, offering internal drainage with fewer tube-related adverse events. In malignant biliary obstruction, transmural drainages are consolidated alternatives of endoscopic retrograde cholangiopancreatography (ERCP) as first-line or rescue strategies, providing durable internal biliary drainage, avoiding post-ERCP pancreatitis without deteriorating quality of life. In surgically altered anatomy, t-EUS overcomes the limitations of enteroscopy-assisted ERCP by creating direct access routes to the biliary tree or pancreatic duct. EUS-guided pancreatic duct drainage offers a rescue or primary approach in benign strictures, anastomotic stenosis, and disconnected duct syndrome. EUS-GE has rapidly become a preferred modality for palliation of gastric outlet obstruction in pancreatic cancer, while EUS-RFA provides a platform for locoregional therapy in selected cases of pancreatic neuroendocrine tumors, adenocarcinoma, and pancreatic cystic neoplasms. Collectively, these applications position t-EUS as a central tool in the multidisciplinary management of complex biliopancreatic disease, with ongoing innovations expected to further expand its indications and safety and to refine patient selection and training pathways. Full article
(This article belongs to the Special Issue Novel Developments in Digestive Endoscopy)
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18 pages, 6900 KB  
Article
The Mechanism of Inhibiting the Adsorption of Rare-Earth Inclusions in Molten Steel by Al2O3, YAlO3 and Y2O3 Refractory by Impressed Current
by Xiaonan Zheng, Diqiang Luo, Chaobin Lai, Hebin Wang and Chao Pan
Metals 2026, 16(4), 413; https://doi.org/10.3390/met16040413 - 9 Apr 2026
Abstract
The adsorption of rare-earth Y-based inclusions (Y, Y2O3, Y2O2S) on Al2O3, YAlO3, and Y2O3 refractory surfaces is a primary cause of nozzle clogging during the continuous [...] Read more.
The adsorption of rare-earth Y-based inclusions (Y, Y2O3, Y2O2S) on Al2O3, YAlO3, and Y2O3 refractory surfaces is a primary cause of nozzle clogging during the continuous casting of rare-earth steels. Conventional anti-clogging strategies, being passive and offline, lack real-time adjustability. This study aims to elucidate the mechanism by which external positive charge modulates interfacial adsorption. Using first-principles calculations combined with partial density of states, charge density difference, and thermodynamic analyses, we investigated the adsorption behavior of Y, Y2O3, and Y2O2S on Al2O3 (001), YAlO3 (001), and Y2O3 (001) surfaces under neutral and positively charged states (+2, +4). A triple inhibition mechanism is revealed: electronically, external charge disrupts O-p and Y-d orbital hybridization, attenuating interfacial covalent bonding; electrostatically, the net positive charge shifts the interfacial interaction from attraction to repulsion, creating a physical barrier; and thermodynamically, the Gibbs free energy change ΔG increases under charged conditions, indicating a quantifiable reduction in adsorption spontaneity. These findings provide a theoretical basis for the development of active anti-clogging strategies in rare-earth steel production. Full article
(This article belongs to the Section Corrosion and Protection)
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19 pages, 3800 KB  
Article
Use of Halogenated Units for the Construction of Artificial Carbohydrate Receptors
by Betty Fuhrmann, Conrad Hübler and Monika Mazik
Molecules 2026, 31(8), 1237; https://doi.org/10.3390/molecules31081237 - 9 Apr 2026
Abstract
To investigate the potential of halogen-containing building blocks in the development of artificial carbohydrate receptors, the 1,3,5-trisubstituted 2,4,6-triethylbenzene scaffold with halogenated subunits and classical hydrogen bonding sites was used as a model system. In the first studies, the influence of the presence of [...] Read more.
To investigate the potential of halogen-containing building blocks in the development of artificial carbohydrate receptors, the 1,3,5-trisubstituted 2,4,6-triethylbenzene scaffold with halogenated subunits and classical hydrogen bonding sites was used as a model system. In the first studies, the influence of the presence of halogens on the binding properties of compounds bearing benzamidomethyl units was investigated, whereby the type of halogen and its ring position were varied. The question was whether the presence of halogens could lead to an increase in binding effectivity and whether this increase can be attributed to the formation of halogen bonds (especially for X = Br and I in ortho position) with the sugar substrate or to other effects. The binding studies revealed some interesting relationships between structure and binding affinity for the tested compounds 19. For those bearing the halogen substituent in the ortho position to the amide functionality, the binding affinity increases in the expected order 4 (o-F) < 3 (o-Cl) < 2 (o-Br) < 1 (o-I). In the presence of small amounts of water in CDCl3, an increase in binding strength was observed in comparison to experiments conducted in dry CDCl3. The present studies aim to provide impulses for the use of halogenated building blocks in the design of artificial carbohydrate receptors. Optimizing the type of halogenated units and the receptor architecture should result in more effective carbohydrate receptors capable of functioning effectively in aqueous media through a combination of different noncovalent interactions. Full article
(This article belongs to the Special Issue Recent Advances in Supramolecular Chemistry, 2nd Edition)
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28 pages, 1987 KB  
Article
Grapevine Ecophysiology: Implications of N Fertilization, Deficit Irrigation, and Arbuscular Mycorrhiza on N Isotope Composition (δ15N)
by Dimitrios Taskos, Georgios Doupis, Serafeim Theocharis, Nikolaos Nikolaou and Stefanos Koundouras
Crops 2026, 6(2), 44; https://doi.org/10.3390/crops6020044 - 9 Apr 2026
Abstract
Over two years, a randomized complete block field trial tested deficit irrigation [I: 70% ETc; NI] and ammonium nitrate [N0, N60, N120; 0, 60, 120 kg N ha−1] application in two northern Greece winegrape vineyards [...] Read more.
Over two years, a randomized complete block field trial tested deficit irrigation [I: 70% ETc; NI] and ammonium nitrate [N0, N60, N120; 0, 60, 120 kg N ha−1] application in two northern Greece winegrape vineyards of cv. ‘Xinomavro’ (XM) and cv. ‘Cabernet Sauvignon’ (CS). Leaf-blade δ15N was measured at berry set, bunch closure, veraison, and technological maturity; berry-juice (must) δ15N at technological maturity and dormant cane δ15N in winter were also determined. In the first year, δ15N was additionally measured in petioles, unripe berries, trunks, and roots, along with arbuscular mycorrhizal fungal (AMF) colonization of fine roots. Fertilization increased δ15N in leaf blades and canes, whereas berry-juice δ15N responded weakly and inconsistently. Irrigation marginally lowered cane δ15N; cane δ15N varied between years, and berry-juice δ15N showed the highest variability across treatments. At berry set, intravine discrimination was evident: young berries and leaf blades were enriched, while fine roots and woody tissues were depleted. Root δ15N responses differed between cultivars and depended on AMF colonization in XM. Leaf and cane δ15N were positively related to vine N status, yield, and pruning weight but negatively to agronomic N-use efficiency indices. These findings indicate that δ15N serves as an integrative proxy of N cycling processes and fertilizer-use efficiency in vineyards, with potential implications for the assessment and optimization of sustainable vineyard management practices in the context of climate change. Full article
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26 pages, 7514 KB  
Article
Meltwater Contribution and Mass Balance of the Juncal Norte Glacier During an Extreme Drought Year in the Dry Andes of Central Chile
by Antonio Bellisario, Jason Janke and Sam Ng
Water 2026, 18(8), 897; https://doi.org/10.3390/w18080897 (registering DOI) - 9 Apr 2026
Abstract
The Juncal Norte Glacier (33°00′ S, 70°06′ W) is in the Dry Andes of central Chile within the Juncal Basin, a headwater watershed of the Aconcagua River, a semi-arid region experiencing an ongoing megadrought since 2010 and a 37% reduction in streamflow relative [...] Read more.
The Juncal Norte Glacier (33°00′ S, 70°06′ W) is in the Dry Andes of central Chile within the Juncal Basin, a headwater watershed of the Aconcagua River, a semi-arid region experiencing an ongoing megadrought since 2010 and a 37% reduction in streamflow relative to pre-1990 baselines. This study provides the first glacier-specific annual melt and runoff estimate for Juncal Norte during mature megadrought conditions. Mass balance was estimated using a temperature index (positive degree day, PDD) model calibrated with automatic weather station (AWS) air temperature data and glacier hypsometry, assuming limited snow accumulation given that 2018–2019 precipitation and snow water equivalent (SWE) were extremely low relative to the long-term mean. Basin runoff was evaluated using a closure method comparing proglacial sub-basin-integrated discharge with modeled glacier melt volumes. Modeled glacier melt for 2018–2019 was equivalent to approximately 30% of observed annual discharge at the proglacial sub-basin, a disproportionate contribution given the glacier covers only 2.7% of the total basin area. The lower ablation zone (2900–4000 m), comprising 30% of glacier area, produced 90% of total melt volume. A + 1 °C temperature perturbation increased glacier-wide melt by 21.4%, confirming high climatic sensitivity. These results underscore the glacier’s critical but increasingly vulnerable buffering role for downstream water availability in the Dry Andes. Full article
(This article belongs to the Section Water and Climate Change)
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26 pages, 2531 KB  
Article
Underwater Acoustic Source DOA Estimation for Non-Uniform Circular Arrays Based on EMD and PWLS Correction
by Chuang Han, Boyuan Zheng and Tao Shen
Symmetry 2026, 18(4), 627; https://doi.org/10.3390/sym18040627 - 9 Apr 2026
Abstract
Uniform circular arrays (UCAs) are widely used in underwater source localization due to their omnidirectional coverage. However, random sensor position errors caused by installation inaccuracies and environmental disturbances convert UCAs into non-uniform circular arrays (NCAs), severely degrading the performance of high-resolution direction of [...] Read more.
Uniform circular arrays (UCAs) are widely used in underwater source localization due to their omnidirectional coverage. However, random sensor position errors caused by installation inaccuracies and environmental disturbances convert UCAs into non-uniform circular arrays (NCAs), severely degrading the performance of high-resolution direction of arrival (DOA) estimation algorithms. To address this issue, this paper proposes a robust DOA estimation method that integrates empirical mode decomposition (EMD) denoising with prior-weighted iterative least squares (PWLS) correction. The method first applies EMD to adaptively denoise received signals by selecting intrinsic mode functions based on a combined energy-correlation criterion. An initial DOA estimate is then obtained using the MUSIC algorithm. Finally, a PWLS correction algorithm leverages prior knowledge of deviated sensors to iteratively fit the circle center and gradually pull sensor positions toward the ideal circumference, using a differentiated relaxation mechanism to suppress outliers while preserving geometric features. Systematic Monte Carlo simulations compare five correction algorithms under multi-frequency and wideband signals. The results show that both multi-frequency and wideband signals reduce estimation errors to below 0.1°, with the proposed PWLS achieving the best accuracy under multi-frequency signals, while all algorithms approach zero error under wideband signals. The PWLS algorithm converges in about 10 iterations with high computational efficiency, providing a reliable solution for practical underwater NCA applications. Full article
(This article belongs to the Section Engineering and Materials)
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27 pages, 2894 KB  
Article
Shengmai San Ameliorates High-Glucose-Induced Calcium Homeostasis Imbalance via Improving Energy Metabolism in Neonatal Rat Cardiomyocytes
by Shixi Shang, Qu Zhai, Yuguo Huang, Junsong Yin, Jingju Wang and Xiaolu Shi
Pharmaceuticals 2026, 19(4), 601; https://doi.org/10.3390/ph19040601 - 8 Apr 2026
Abstract
Objective: This study aims to investigate the protective effect of Shengmai San (SMS) against high-glucose (HG)-induced injury in neonatal rat ventricular myocytes (NRVMs) and to elucidate the underlying pharmacological molecular mechanisms. We hypothesize that SMS ameliorates HG-induced calcium homeostasis imbalance in NRVMs by [...] Read more.
Objective: This study aims to investigate the protective effect of Shengmai San (SMS) against high-glucose (HG)-induced injury in neonatal rat ventricular myocytes (NRVMs) and to elucidate the underlying pharmacological molecular mechanisms. We hypothesize that SMS ameliorates HG-induced calcium homeostasis imbalance in NRVMs by improving mitochondrial energy metabolism disorder, and this protective effect is associated with the downregulation of oxidized and phosphorylated CaMKII expression to inhibit CaMKII signaling pathway overactivation. Herein, we verify this hypothesis by assessing mitochondrial function, calcium transients, sarcoplasmic reticulum (SR) calcium handling and CaMKII phosphorylation levels in NRVMs. Methods: First, ultra-high performance liquid chromatography–high resolution mass spectrometry was used to identify the chemical components of SMS to clarify its material basis. Primary NRVMs were then cultured under low-glucose (LG) or HG conditions, with 2% SMS-medicated serum (SMS-MS) as the experimental intervention, and NAC (ROS scavenger) and KN93 (CaMKII inhibitor) as positive controls. Following intervention, we sequentially detected key indicators corresponding to the proposed pathological pathway: intracellular reactive oxygen species (ROS) levels (oxidative stress), mitochondrial ROS, mitochondrial function indices including oxygen consumption rate (OCR) (energy metabolism), calcium transients and diastolic intracellular free calcium concentration (global calcium homeostasis), sarcoplasmic reticulum (SR) calcium leak (calcium handling disorder), and, finally, the phosphorylation, oxidation levels of CaMKII and RyR2 phosphorylation (Ser2814) (p-RyR2) (key regulatory pathway) via Western blot to systematically elucidate the mechanistic link between SMS intervention and HG-induced NRVM injury. Results: Quantitative analysis revealed that high-glucose (HG) induction significantly reduced calcium transient amplitude and prolonged the decay time constant (tau) in NRVMs at 72 h (p < 0.01 vs. LG), with these parameters normalizing by 120 h—an effect indicative of a compensatory adaptive response. The 2%SMS-MS markedly ameliorated HG-induced calcium transient abnormalities at 72 h (p < 0.01 vs. HG). Additionally, 2%SMS-MS significantly enhanced mitochondrial basal oxygen consumption rate, spare respiratory capacity, ATP production, and maximal respiration in HG-exposed NRVMs (p < 0.01 vs. HG). SMS also significantly reduced intracellular reactive oxygen species (ROS) levels (p < 0.01 vs. HG), mitochondrial ROS levels (p < 0.01 vs. HG), diastolic intracellular free calcium concentration (p < 0.01 vs. HG), and SR calcium leak (p < 0.05 vs. HG). Western blot analysis revealed that 2%SMS-MS intervention effectively downregulated the expression of oxidized CaMKII (Ox-CaMKII) (p < 0.01 vs. HG), phosphorylated CaMKII (p-CaMKII) (p < 0.01 vs. HG), and RyR2 phosphorylation (Ser2814) (p < 0.05 vs. HG), which may be the potential mechanism in maintaining calcium homeostasis in HG-induced NRVMs. Conclusions: This study suggests that SMS enhances mitochondrial energy metabolism and exerts a protective effect against high-glucose-induced calcium homeostasis imbalance in NRVMs, which supports our proposed hypothesis. Its potential mechanism indicates that the protective effects of SMS are associated with its ability to downregulate the expression of oxidized and phosphorylated CaMKII. These findings highlight SMS as a potential therapeutic candidate for alleviating HG-related myocardial injury and provide evidence for its application in the prevention of early diabetic cardiomyopathy. Full article
(This article belongs to the Section Pharmacology)
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